Homology Model and Docking-Based Virtual Screening for Ligands of the σ1 Receptor
Homology Model and Docking-Based Virtual Screening for Ligands of the σ1 Receptor
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DOI：
10.1021/ml2001505
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发表时间：
2011-11-01
影响因子：
4.2
通讯作者：
Pricl, Sabrina
中科院分区：
文献类型：
--
作者：
Laurini, Erik;Dal Col, Valentina;Pricl, Sabrina
这项研究首次提出了从同源建模技术获得的sigma（1）受体蛋白的3D模型，显示了这种结构对基于对接的虚拟筛选的适用性，定义了一种基于3D药效团对接和MM/PBSA结合自由能评分组合的计算策略来优化结果，并提供证据表明，这些计算机模型和配方是虚拟筛选新σ（1）配体的有力工具。特别是，基于对接的虚拟筛选同源性模型的适用性的验证是极其重要的，因为迄今为止没有晶体结构可用于sigma（1）受体，并且这种缺失的信息仍然构成了用于该重要蛋白质靶的合理配体设计的主要障碍。
This study presents for the first time the 3D model of the sigma(1) receptor protein as obtained from homology modeling techniques, shows the applicability of this structure to docking-based virtual screening, defines a computational strategy to optimize the results based on a combination of 3D pharmacophore-based docking and MM/PBSA free energy of binding scoring, and provides evidence that these in silico models and recipes are powerful tools on which virtual screening of new sigma(1) ligands can be based. In particular, the validation of the applicability of docking-based virtual screening to homology models is of utmost importance, since no crystal structure is available to date for the sigma(1) receptor, and this missing information still constitutes a major hurdle for a rational ligand design for this important protein target.